ZIKV is a non-segmented, single stranded positive sense RNA virus belonging to the family Flaviviridae in the genus Flavivirus. It is enveloped and icosahedral and it is related to dengue, yellow fever and West Nile virus. ZIKV is spread primarily by mosquitoes in the Aedes genus, primarily Aedes aegypti. However, ZIKV can also be spread in the human population by sexual transmission, even in circumstances where the infected partner has no symptoms of infection. ZIKV can be found in the sperm of infected subjects for up to six months following infection thus creating a longterm risk of exposure for partners and unborn children. ZIKV can also be transmitted through blood transfusion.
ZIKV causes infection in humans, which causes fever, rash, joint pain and headache. Although the symptoms of Zika fever are mild in most patients, infection in adults has been associated with rare cases of Guillain-Barre Syndrome, an autoimmune disease causing muscle weakness, pain and even death (Cor-Lormeau et al., 2016, Lancet 387: 1531-39). Furthermore, infection during pregnancy has been associated with microcephaly, and other severe brain malformations in some babies including loss of normal brain tissue, abnormal brain folding and calcification (infection-related scarring) (Soares de Oliveira-Szeinfeld et al., 2016, Radiology 281: 203-218). ZIKV exposure in utero has also be linked to eye defects, hearing loss and impaired growth. Recent studies in mice have shown that ZIKV infection causes damage to the testes of male mice with a resulting reduction in sperm count and reduced rates of pregnancy in female mice mated with the ZIKV-infected males (Govero, J. et al., (2016) Nature 540: 438-448).
ZIKV was first discovered in a monkey in Uganda in 1947 and was identified in humans shortly thereafter. Sporatic outbreaks occurred in Africa and Asia in the 1960's and 1980's. Between 2007 and 2013, outbreaks occurred in Micronesia and Oceania. Three separate lineages of ZIKV have been identified, two associated with the African outbreaks and one associated with the Asian outbreak. In 2015, an outbreak began in Brazil which quickly spread through 25 additional countries in South America and the Caribbean islands with alarming rates of microcephaly reported (Samarasekera et al., 2016, Lancet 387: 521-524). In January, 2016, the U.S. National Institutes of Health confirmed that the ZIKV outbreak in South America and the Caribbean had reached pandemic levels. On Feb. 1, 2016, the World Health Organization declared the clusters of microcephaly and neurological disorders and their association with ZIKV to be a global public health emergency. In 2016, ZIKV cases were reported in the US states of Florida and Texas which were acquired by local mosquito-borne transmission.
Vaccines have been developed for other flaviruses including yellow fever virus and dengue infection. However, prior to the outbreak of the ZIKV epidemic in the Americas in 2015, little was known about ZIKV immunology. There is currently no commercially available vaccine available for ZIKV.
In June of 2016, the Walter Reed Army Institute of Research and Harvard Medical School published the results of immunological studies using two different vaccine candidates, one a plasmid DNA vaccine and one a purified inactivated virus (PIV) vaccine derived from a ZIKV strain from Puerto Rico (Larocca et al., 2016, Nature: doi:10.1038). Both vaccines were shown to induce ZIKV specific neutralizing antibodies after a single immunization. These results have demonstrated that it is possible to formulate a vaccine to ZIKV which will induce an immunogenic response. However, no vaccine has yet been shown to be a strong candidate for a human ZIKV vaccine. Plasmid DNA vaccines have proven to be poorly immunogenic in clinical trials in humans (Ferraro et al., 2011, Clin. Infec. Dis. 53: 296-302). Inactivated virus vaccines frequently show a weak immune response in humans, thus requiring the use of multiple booster injections, which may be impractical to track and deliver in developing countries. Furthermore, inactivated vaccines can have adverse side effects.
Accordingly, a need exists for a vaccine against ZIKV.